The mechanism of production of malignant transformation by carcinogenic polycyclic hydrocarbon in a cell culture model system will be explored in this project through the application of a series of specific, but highly interdependent, investigations. These studies will involve utilization of cloned cell lines derived from mouse embryos for induction of stable phenotypic changes by chemical carcinogen. Non-transformed and transformed populations of cells will be characterized with respect to chromatin template capacity for DNA-dependent RNA synthesis, and level of endogenous RNA polymerase activity. The studies on these cell culture model systems will examine macromolecular binding of carcinogenic and non-carcinogenic polycyclic hydrocarbons in the nucleus where binding to the various components of chromatin will be examined. An attempt will be made to identify the actual compounds bound to chromatin and to determine the transforming capabilities of these compounds extracted from chromatin in the presence and absence of aryl hydrocarbon hydroxylase inhibitors. The acute effects of these polycyclic hydrocarbons on nuclear endogenous RNA polymerase activities, chromatin template capacity, and nuclear acidic protein synthesis and degradation will be studied. The studies will also include an examination of the effects of carcinogen metabolism on intracellular macromolecular binding and induced alterations in transcriptional events. BIBLIOGRAPHIC REFERENCES: Zytkovicz, T., Moses, H.L. and Spelsberg, T.C.: High affinity binding of chemical carcinogen specific sites in mouse cell nuclei. Fed. Proc. 35:1707, 1976. Getz, M.J., Elder, P.K., Benz, E.W., Jr., Stephens, R.E. and Moses, H.L.: Effect of cell proliferation on levels and diversity of poly(A)-containing mRNA. Cell. 7:255-265, 1976.